Inhibitors of cell membrane

Dr. Abdulrahman T. Saadi

Assistant professor of Medical
Microbiology
 Introduction
• The cytoplasm of all living cells is bounded by the
cytoplasmic membrane.
• It serves as a selective permeability barrier, carries
out active transport functions, and thus controls the
internal composition of the cell.
• The cytoplasmic membrane is involved in a variety
of cellular processes such as cell adhesion, ion
conductivity, and cell signalling.
 Bacterial cytoplasmic membrane
• The cytoplasmic membrane of bacteria and fungi has a
structure different from that of animal cells and if its
functional integrity is disrupted cell damage or death results
• Several antimicrobials bind to the outer membrane
disrupting the plasma membrane causes:
– rapid depolarization
– loss of membrane potential
– inhibition of protein, DNA and RNA synthesis
• Block passage of solutes resulting in bacterial toxicity and
cell death.
 Polymyxin B and polymyxin E (Colistin)
• They are a group of polypeptide that are active against gram
negative bacteria but inactive for gram positive bacteria.
• Polymyxin B is administered parenterally in its active form,
while colistin is administered parenterally as an inactive form
• Because of their nephrotoxic and neurotoxic side effects and
poor distribution to tissues, polymyxins were used primarily
topically and are rarely used for systemic infections.
• With the emergence of multi-resistant gram negative organisms,
injectable polymyxins are in use again.
 Polymyxins: mode of action

• Polymyxins can be bactericidal for many gram-negative

aerobic rods by binding to cell membranes rich in
phospholipids (phosphatidyl ethanolamine).
• They destroy membrane functions of active transport
and permeability barrier.
• They bind and neutralize lipopolysaccharides and may
prevent the pathophysiologic effects of endotoxin in the
circulation.
 Polymyxin B
• Polymyxin B offers multiple pharmacokinetic advantages
in the treatment of systemic infections:
– Polymyxin B achieves therapeutic concentrations rapidly.
– Provides more predictable serum concentrations.
• Lower rates of nephrotoxicity with polymyxin B compared
with colistin.
• Resistance eventually developed following treatment with
either agent.
• This supports the importance of using both polymyxins
only in combination with additional antibiotics and
(almost) never as monotherapy.
 Uses of Polymyxin B
• 1. Treatment of severe infections caused by multi-
drug resistant Gram negative organisms. Examples:
ventilator associated pneumonia caused by
Pseudomonas aereuginosa.
• 2. Decontamination of the gastro-intestinal tract in
high risk patients: leukaemic and intensive care
patients.
 Polymyxin E (colistin)
• Available topically and parenterally, not used orally.
• Poor penetration of CSF, pleural fluid and biliary tract.
• Colistin is bactericidal against these gram-negative
organisms. When used wisely, observed toxicity has been
less than previously described.
• It is used for:
– Treatment of multidrug resistant bacilli: Acinetobacter
baumannii and P. aereuginosa
– Therapy for carbapenemase-resistant Klebsiella infections.
 Bacitracin

• Bacitracin is a polypeptide obtained from a strain of

Bacillus subtilis.
• It is stable and poorly absorbed from the intestinal tract.
• Bacitracin is used to help prevent minor skin injuries such
as cuts, scrapes, and burns from becoming infected.
• Bacitracin is mainly bactericidal for gram-positive
bacteria, including penicillin-resistant staphylococci.
 Clinical uses of Bacitracin
• 1. Its only use is for topical application to skin,
wounds, or mucous membranes. Do not use this
medication to treat deep cuts, puncture wounds,
animal bites, serious burns, or any injuries that affect
large areas of your body.
• 2. In combination with polymyxin B or neomycin,
bacitracin is useful for the suppression of mixed
bacterial flora in surface lesions.
 Bacitracin
• It is used in diagnostic laboratory to identify
Streptococcus pyogenes which is bacitracin
sensitive.
• Side effects: Bacitracin is toxic for the kidney,
causing proteinuria, haematuria, and nitrogen
retention. For this reason, it has no place in
systemic therapy.